Rac2 enhances activation of microglia and astrocytes, inflammatory response, and apoptosis via activating JNK signaling pathway and suppressing SIRT1 expression in chronic constriction injury-induced neuropathic pain
Abstract Neuropathic pain (NP) is pain caused by injury or dysfunction of the somatosensory system. The role of Rac2, a member of the Rac family, which is expressed in neutrophils, macrophages, and adult T cells, in NP remains unclear. Using a chronic constriction injury (CCI)-induced NP model in ra...
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Veröffentlicht in: | Journal of neuropathology and experimental neurology 2023-05, Vol.82 (5), p.419-426 |
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description | Abstract
Neuropathic pain (NP) is pain caused by injury or dysfunction of the somatosensory system. The role of Rac2, a member of the Rac family, which is expressed in neutrophils, macrophages, and adult T cells, in NP remains unclear. Using a chronic constriction injury (CCI)-induced NP model in rats, we found that Rac2 expression was elevated in rats with CCI-induced NP and that overexpression of Rac2 aggravated the NP. Rac2 overexpression also aggravated the inflammatory response, induced activation of microglia and astrocytes, and enhanced apoptosis whereas knockdown of Rac2 had the opposite effects. Rac2 suppressed SIRT1 expression via activating the c-Jun N-terminal kinase (JNK) signaling pathway. In rescue experiments, SRT1720, an activator of SIRT1, reversed the effect of Rac2 on glial activation, inflammatory response, and apoptosis. These findings indicate that Rac2 enhances the activation of microglia and astrocytes, inflammatory response, and apoptosis via activating the JNK signaling pathway and suppressing SIRT1 expression in CCI-induced NP. |
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Neuropathic pain (NP) is pain caused by injury or dysfunction of the somatosensory system. The role of Rac2, a member of the Rac family, which is expressed in neutrophils, macrophages, and adult T cells, in NP remains unclear. Using a chronic constriction injury (CCI)-induced NP model in rats, we found that Rac2 expression was elevated in rats with CCI-induced NP and that overexpression of Rac2 aggravated the NP. Rac2 overexpression also aggravated the inflammatory response, induced activation of microglia and astrocytes, and enhanced apoptosis whereas knockdown of Rac2 had the opposite effects. Rac2 suppressed SIRT1 expression via activating the c-Jun N-terminal kinase (JNK) signaling pathway. In rescue experiments, SRT1720, an activator of SIRT1, reversed the effect of Rac2 on glial activation, inflammatory response, and apoptosis. These findings indicate that Rac2 enhances the activation of microglia and astrocytes, inflammatory response, and apoptosis via activating the JNK signaling pathway and suppressing SIRT1 expression in CCI-induced NP.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1093/jnen/nlad006</identifier><identifier>PMID: 36779914</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Apoptosis ; Astrocytes ; Astrocytes - metabolism ; Cellular signal transduction ; Constriction ; Development and progression ; Guanosine triphosphatase ; Health aspects ; Inflammation ; MAP Kinase Signaling System ; Microglia - metabolism ; Neuralgia ; Neuralgia - etiology ; Neuralgia - metabolism ; Neurological research ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1 - genetics ; Sirtuin 1 - metabolism ; Sirtuin 1 - pharmacology</subject><ispartof>Journal of neuropathology and experimental neurology, 2023-05, Vol.82 (5), p.419-426</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.</rights><rights>COPYRIGHT 2023 Oxford University Press</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-e3d55d3abc6f14a8c57126e80f791c759cca4c91bd168d71d21370f7752809143</citedby><cites>FETCH-LOGICAL-c418t-e3d55d3abc6f14a8c57126e80f791c759cca4c91bd168d71d21370f7752809143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,1585,27928,27929</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36779914$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>An, Min</creatorcontrib><creatorcontrib>Qiu, Yi</creatorcontrib><creatorcontrib>Wang, Caixia</creatorcontrib><creatorcontrib>Ma, Penglei</creatorcontrib><creatorcontrib>Ding, Yumei</creatorcontrib><title>Rac2 enhances activation of microglia and astrocytes, inflammatory response, and apoptosis via activating JNK signaling pathway and suppressing SIRT1 expression in chronic constriction injury-induced neuropathic pain</title><title>Journal of neuropathology and experimental neurology</title><addtitle>J Neuropathol Exp Neurol</addtitle><description>Abstract
Neuropathic pain (NP) is pain caused by injury or dysfunction of the somatosensory system. The role of Rac2, a member of the Rac family, which is expressed in neutrophils, macrophages, and adult T cells, in NP remains unclear. Using a chronic constriction injury (CCI)-induced NP model in rats, we found that Rac2 expression was elevated in rats with CCI-induced NP and that overexpression of Rac2 aggravated the NP. Rac2 overexpression also aggravated the inflammatory response, induced activation of microglia and astrocytes, and enhanced apoptosis whereas knockdown of Rac2 had the opposite effects. Rac2 suppressed SIRT1 expression via activating the c-Jun N-terminal kinase (JNK) signaling pathway. In rescue experiments, SRT1720, an activator of SIRT1, reversed the effect of Rac2 on glial activation, inflammatory response, and apoptosis. These findings indicate that Rac2 enhances the activation of microglia and astrocytes, inflammatory response, and apoptosis via activating the JNK signaling pathway and suppressing SIRT1 expression in CCI-induced NP.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Astrocytes</subject><subject>Astrocytes - metabolism</subject><subject>Cellular signal transduction</subject><subject>Constriction</subject><subject>Development and progression</subject><subject>Guanosine triphosphatase</subject><subject>Health aspects</subject><subject>Inflammation</subject><subject>MAP Kinase Signaling System</subject><subject>Microglia - metabolism</subject><subject>Neuralgia</subject><subject>Neuralgia - etiology</subject><subject>Neuralgia - metabolism</subject><subject>Neurological research</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sirtuin 1 - genetics</subject><subject>Sirtuin 1 - metabolism</subject><subject>Sirtuin 1 - pharmacology</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kk9v1DAQxSMEokvhxhlZ4kAPm9bOPyfHqqJQqEAq5RzN2pNdrxLbtZ1CvikfB4csCBBCPlge_96zNfOS5Dmjp4w2-dleoz7TPUhKqwfJipVlkVYlrx8mK0qzLM1p1RwlT7zfU0ob2hSPk6O84rxpWLFKvt2AyAjqHWiBnoAI6h6CMpqYjgxKOLPtFRDQkoAPzogpoF8TpbsehgGCcRNx6K3RHtcLZo0NxitP7mfhwVBvybsP74lXWw39fLIQdl9g-iHxo7XRxM_1T1c3t4zg16UQ_6E0ETtntBJExFeCUyIs9f3oplRpOQqUROPozGwaOQtKP00eddB7fHbYj5PPl69vL96m1x_fXF2cX6eiYHVIMZdlKXPYiKpjBdSi5CyrsKYdb5jgZSMEFKJhG8mqWnImM5bzeMnLrKaxg_lxcrL4WmfuRvShHZQX2Peg0Yy-zSLalHEILKIv_0L3ZnSxH77NacnqrKD1b9QWemxjo01wIGbT9pxXdZEVcYiROv0HFZfEODWjsVOx_odgvQjiSL132LXWqQHc1DLazkFq5yC1hyBF_MXhr-NmQPkL_pmcCLxaADPa_1t9Bx311oI</recordid><startdate>20230501</startdate><enddate>20230501</enddate><creator>An, Min</creator><creator>Qiu, Yi</creator><creator>Wang, Caixia</creator><creator>Ma, Penglei</creator><creator>Ding, Yumei</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20230501</creationdate><title>Rac2 enhances activation of microglia and astrocytes, inflammatory response, and apoptosis via activating JNK signaling pathway and suppressing SIRT1 expression in chronic constriction injury-induced neuropathic pain</title><author>An, Min ; Qiu, Yi ; Wang, Caixia ; Ma, Penglei ; Ding, Yumei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-e3d55d3abc6f14a8c57126e80f791c759cca4c91bd168d71d21370f7752809143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Astrocytes</topic><topic>Astrocytes - metabolism</topic><topic>Cellular signal transduction</topic><topic>Constriction</topic><topic>Development and progression</topic><topic>Guanosine triphosphatase</topic><topic>Health aspects</topic><topic>Inflammation</topic><topic>MAP Kinase Signaling System</topic><topic>Microglia - metabolism</topic><topic>Neuralgia</topic><topic>Neuralgia - etiology</topic><topic>Neuralgia - metabolism</topic><topic>Neurological research</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sirtuin 1 - genetics</topic><topic>Sirtuin 1 - metabolism</topic><topic>Sirtuin 1 - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>An, Min</creatorcontrib><creatorcontrib>Qiu, Yi</creatorcontrib><creatorcontrib>Wang, Caixia</creatorcontrib><creatorcontrib>Ma, Penglei</creatorcontrib><creatorcontrib>Ding, Yumei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuropathology and experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>An, Min</au><au>Qiu, Yi</au><au>Wang, Caixia</au><au>Ma, Penglei</au><au>Ding, Yumei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rac2 enhances activation of microglia and astrocytes, inflammatory response, and apoptosis via activating JNK signaling pathway and suppressing SIRT1 expression in chronic constriction injury-induced neuropathic pain</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><addtitle>J Neuropathol Exp Neurol</addtitle><date>2023-05-01</date><risdate>2023</risdate><volume>82</volume><issue>5</issue><spage>419</spage><epage>426</epage><pages>419-426</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><abstract>Abstract
Neuropathic pain (NP) is pain caused by injury or dysfunction of the somatosensory system. The role of Rac2, a member of the Rac family, which is expressed in neutrophils, macrophages, and adult T cells, in NP remains unclear. Using a chronic constriction injury (CCI)-induced NP model in rats, we found that Rac2 expression was elevated in rats with CCI-induced NP and that overexpression of Rac2 aggravated the NP. Rac2 overexpression also aggravated the inflammatory response, induced activation of microglia and astrocytes, and enhanced apoptosis whereas knockdown of Rac2 had the opposite effects. Rac2 suppressed SIRT1 expression via activating the c-Jun N-terminal kinase (JNK) signaling pathway. In rescue experiments, SRT1720, an activator of SIRT1, reversed the effect of Rac2 on glial activation, inflammatory response, and apoptosis. These findings indicate that Rac2 enhances the activation of microglia and astrocytes, inflammatory response, and apoptosis via activating the JNK signaling pathway and suppressing SIRT1 expression in CCI-induced NP.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>36779914</pmid><doi>10.1093/jnen/nlad006</doi><tpages>8</tpages></addata></record> |
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subjects | Animals Apoptosis Astrocytes Astrocytes - metabolism Cellular signal transduction Constriction Development and progression Guanosine triphosphatase Health aspects Inflammation MAP Kinase Signaling System Microglia - metabolism Neuralgia Neuralgia - etiology Neuralgia - metabolism Neurological research Rats Rats, Sprague-Dawley Sirtuin 1 - genetics Sirtuin 1 - metabolism Sirtuin 1 - pharmacology |
title | Rac2 enhances activation of microglia and astrocytes, inflammatory response, and apoptosis via activating JNK signaling pathway and suppressing SIRT1 expression in chronic constriction injury-induced neuropathic pain |
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